Abdominal Aortic Aneurysms: Basic Mechanisms and Clinical Implications
Section snippets
Ruptured AAAs
Most AAAs do not cause symptoms until late in their natural history, when they have the potential for spontaneous rupture. Ruptured AAAs represent an immediate emergency, with an overall mortality rate greater than 90%. This is due to the fact that substantial intra-abdominal hemorrhage is often accompanied by delays in transport and diagnosis and the need for emergency operation in elderly individuals, who frequently have significant cardiopulmonary and renal comorbidity. Even with prompt
Structure of the normal aorta
The vertebrate aorta is responsible for efficiently transmitting pulsatile arterial blood pressure to all points in the arterial tree, a function that depends primarily on its properties as an elastic conduit. The aorta must also bear a continuous mechanical load and thereby retain its functional capacity over a lifetime of hemodynamic wall stress. The aortic wall therefore requires the properties of resilience to cyclic deformation, of resistance to structural failure, and of durability over
Pathophysiologic processes in aneurysmal degeneration
One of the important concepts that has emerged over the past 2 decades is that aneurysm disease represents a complicated and dynamic pathophysiologic process rather than a static pathologic problem; moreover, AAAs develop insidiously and expand gradually over time (Fig 1). Knowledge of the pathophysiologic processes that determine the course of aneurysmal degeneration is a crucial step toward understanding this disease in sufficient detail to develop new therapeutic strategies. The following
SMC apoptosis and senescence
Although increased proteolytic activity is now widely accepted as a major factor in the pathogenesis of AAAs, it is also becoming apparent that impaired connective tissue repair may also be critically important, either in the gradual progression of disease or in precipitating aneurysm rupture. The stability of established AAAs is likely dependent on a substantial increase in collagen production, given the enormous increase in tensile wall stress as the aorta dilates. Adventitial fibroblasts and
The interface between biomechanics and molecular biology
Given the importance of elastin and collagen in aortic wall structure and the biophysical demands placed on the aortic wall during aneurysmal dilatation, it is somewhat perplexing that AAAs should develop slowly and expand in a gradual fashion, rather than develop instantaneously with immediate rupture. It is therefore informative to ask why aneurysms do not rupture earlier in their natural history, or what factors trigger rupture in previously stable lesions. An understanding for these
Lessons learned from animal models
Studies using animal models of AAAs have provided important insights into the pathophysiologic features of AAAs, particularly in the past decade. These experimental systems have also provided essential tools to evaluate the potential for new therapeutic strategies to suppress aneurysmal degeneration in vivo. Although the present discussion is focused on models with which the authors have direct experience and greatest familiarity, interested readers will find more detail on other models in
T: Pharmacologic strategies and biomarkers
Despite the enthusiasm surrounding basic knowledge and new pathophysiologic concepts of aneurysm disease, no therapeutic approaches have proved to reduce the rate of aneurysm expansion in patients. Given that several pharmacologic strategies effectively suppress aneurysmal degeneration in animal models of AAAs, 1 of the challenges for the next several years will be to translate these findings to clinical application.
A blueprint for further investigation
The primary goal of this review has been to provide a current summary of basic and translational research on aortic aneurysm disease and to gain some insight into the therapeutic implications that this work may yield in the near future. Although a review of this type can provide valuable background information and a synopsis of current knowledge, it is intrinsically limited by the scope of what lies immediately ahead. This is particularly evident in the current atmosphere of biomedicine and
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